1. Field of the Invention
The present invention relates to a method of detecting the presence of a target bio-molecule or a concentration of the respective bio-molecules using a field effect transistor.
2. Description of the Related Art
A transistor based bio-sensor which includes a transistor is one kind of sensor that detects bio-molecules using electric signals. A semiconductor process is used to manufacture the transistor based bio-sensor, and thus the electric signals can be quickly converted in the transistor based bio-sensor. Accordingly, much research on this kind of sensor has been carried out.
U.S. Pat. No. 4,238,757 discloses a field effect transistor (FET) that can be used to detect biological reactions. Using the FET, a bio-sensor measures a current change in an inversion layer of a semiconductor resulting from changes in the surface charge concentration in order to detect an antigen-antibody reaction. By employing a bio-sensor using the FET, the presence of a protein among the bio-molecules can be detected. U.S. Pat. No. 4,777,019 discloses a sensor for measuring a hybridization of biological monomers with complementary monomers by adsorbing the biological monomers onto the surface of a gate using a FET.
U.S. Pat. No. 5,846,708 discloses a method of determining the presence of hybridization by an extinction of coupled bio-molecules using a charged couple device (CCD). U.S. Pat. Nos. 5,466,348 and 6,203,981 disclose a method of increasing a ratio of signal to noise using a thin film transistor (TFT) with a circuit.
The use of the FET as a bio-sensor decreases costs and reduces the amount of time required to detect the bio-molecules, and the FET is easily used together with a process including an integrated circuit (IC)/MEMS.
FIG. 1A represents the prior art and schematically illustrates the structure of a conventional FET. Referring to the FIG. 1A, the FET includes a substrate 11 doped with an n-type or a p-type material, a source 12a and a drain 12b which are formed on both sides of the substrate 11 and doped to have the opposite polarity to the substrate 11, and a gate 13 on the substrate 11 that is in electrical communication with the source 12a and the drain 12b. Generally, the gate 13 includes an oxide layer 14, a poly silicon layer 15, and a gate electrode 16. Probe bio-molecules generally adhere to a surface 16a of the gate electrode 16, which face a reference electrode 17. The probe bio-molecule binds to a target bio-molecule through a hydrogen bond, or the like, and the bond is detected using an electrical method by the amount of electricity generated between the gate electrode 16 and the reference electrode 17.
FIG. 1B schematically illustrates a process of immobilizing probe bio-molecules 18 on a surface 16a of a gate electrode 16 of the FET illustrated in FIG. 1A and binding target bio-molecules with the probe bio-molecules 18. Referring to FIG. 1B, a current flowing through a channel varies according to the presence of the immobilized probe bio-molecules 18 on the surface of the gate electrode 16 and the presence of the bond between immobilized probe bio-molecules 18 and the target bio-molecules, and thus the target bio-molecules can be detected.
In general, more than two FETs are used to improve accuracy and sensitivity in a conventional method for detecting bio-molecules using the FET. Some of the FETs are used as reference FETs that do not react with the target bio-molecules and the others are used as sensing FETs that react with the target bio-molecules. The electric signal of the target bio-molecules can be obtained by subtracting the electric signals measured by the reference FETs from the electric signals measured in the sensing FETs on the assumption that noise signals are the same in the reference FETs and the sensing FETs.
For example, International Publication No. WO 03/062811 discloses a method of inferring a representative factor from comparing the data measured by two different sensors.
However, the assumption that noise signals are the same in the reference FETs and the sensing FETs is not reliable. In other words, although the FETs are manufactured by the same process to meet the same standard requirements, a wide range of variation occurs in the present FET manufacturing technology. Thus, the electric signals of the reference FET may be greater than that of the sensing FET.